This project is a study of the pharmacological and toxicological properties of the anthraquinone cathartics. Danthron is the prototype to be investigated, in guinea pigs, mice and rats. Anthraquinones are capable of causing melanosis coli, colonic smooth muscle atrophy and myenteric plexus degeneration. Therefore, we plan a quantitative analysis of absorption, distribution, metabolism (both hepatic and intestinal bacterial), and elimination of danthron. Correlated with this will be a quantitative morphological study of the dose and time parameters necessary to produce melanosis, and colonic neuro- and myotoxicity. These pathological changes will be investigated by light, fluorescence and electron microscopy to clarify the pathogenesis and the toxic principle(s), i.e. whether parent drug or metabolite. We will also determine if the cathartic and neurotoxic effects of anthraquinones vary with intake of vitamin C (ascorbic acid).